When they were boys, Sam and Dean Winchester lost their mother to a mysterious and demonic supernatural force. Subsequently, their father raised them to be soldiers. He taught them about the paranormal evil that lives in the dark corners and on the back roads of America ... and he taught them how to kill it. Now, the Winchester brothers crisscross the country in their '67 Chevy Impala, battling every kind of supernatural threat they encounter along the way.

Castiel finds Jimmy’s daughter Claire in a group home and she convinces him to break her out. After she runs away from him, Castiel calls Sam and Dean to help find her before she gets in trouble. Meanwhile, Crowley faces his biggest challenge yet.

After the massacre at the ranch, Dean, Sam, and Castiel double their efforts to find a cure for the Mark of Cain but there is nothing in the lore that can help them. Desperate, Castiel comes up with an idea that Sam deems the "single worst idea I've ever heard." Meanwhile, Rowena continues to plot against Crowley, and Castiel tries to mend his relationship with Claire who is plotting revenge against Dean for killing her friend.

Sam is scanning the internet for suspicious paranormal activity and comes across a video of Charlie beating up a district attorney. Dean suspects she’s back from Oz and hunting on her own, assuming the district attorney must have been a demon. When they do find Charlie, they are shocked when she tells them why she really came back from Oz.

A ghost starts killing people through various electronic devices. Sam and Dean discover who was killed and why this ghost is seeking revenge on a group of college students but what they can't figure out is how he’s doing it. With three dead, the brothers must stop the ghost before he claims his next victim.

Despite Dean's directive to forget about looking for a cure for the Mark of Cain, Sam continues to do research. Dean suspects Sam is hiding something but decides to focus on a new murder case where they run into Cole. The three team up and learn a Khan worm is infecting men and turning them into murderers. Unfortunately, the worm makes its way into Cole.

Sam and Dean investigate a string of suicides committed by people with little in common other than the identical, grisly method of death – slow, self-administered disembowlment. All of the victims were members of a Catholic church and had recently given confession, leading the brothers to suspect the priest is somehow involved. Meanwhile, when Crowley captures Olivette, the leader of the Grand Coven, Rowena pleads her case to be allowed to practice magic freely again.

Charlie calls Sam and Dean to tell them she found the Book of the Dead which could help remove the Mark of Cain. The Winchesters race to her after she tells them she’s been shot by a man named Jacob Styne who says the book belongs to his family and he won’t rest until he gets it back. Castiel and Metatron take a road trip to find Castiel’s grace but they hit a couple road bumps along the way.

Sam learns that former Men of Letters, Magnus, once built a magical box and Sam sets out to find it in the hopes it can cure Dean of the Mark of Cain. However, what he’s not prepared for is the deadly alarm system Magnus set up on the box. When Sam opens the box, he puts both his and Dean’s life in danger.

When Claire Novak gets a lead on her mother, Amelia, who has been missing for years, Castiel asks Sam and Dean to help her. Castiel feels guilty for what he did to the Novak family and wants to make amends by reuniting Claire with her mom. However, when they find out what took Amelia, they realize there is a chance Claire may not get her happy ending.

Dean and Sam investigate a bizarre murder and realize the killer bears the same tattoo as those from the Styne family. Eldon Styne attacks Dean and a brutal fight ensues. Meanwhile, Castiel acts as referee when Charlie and Rowena are forced to work together on the Book of the Damned. Crowley discovers his mother is missing and knows she's up to something so he turns to an old enemy for help.